Joubert Syndrome in Three Children in A Family: A Case Series

Joubert syndrome (JS) is a rare autosomal recessive central nervous system malformation characterized by hypoplasia of the cerebellar vermis, hypotonia and abnormal psychomotor development, along with altered respiratory pattern and various ophthalmologic features. Here, we describe three children with Joubert syndrome in a family that had almost similar presentations, including ataxia, developmental delay, mental retardation and ocular disorders. Prevalence of Joubert syndrome is about 1 in 100,000 live birth. It may be accompanied by other organs’ disorders. The molar tooth sign is pathognomonic for joubert syndrome that is ascertained by brain MRI.


Introduction
Joubert syndrome (JS) is a rare autosomal recessive central nervous system malformation characterized by hypoplasia of the cerebellar vermis, hypotonia and abnormal psychomotor development, together with altered respiratory pattern and various ophthalmologic features (1). Other common characteristics of this syndrome are ataxia, oculomotor apraxia, developmental delay and mental retardation (2). Estimates of the incidence of JS ranges between 1/80,000 and 1/100,000 live births and its recurrence risk is 25% in most families (3). Renal insufficiency is rarely reported in JS (4). Location of the affected gene of this disorder has not been definitely identified (5), so, clinical and radiological signs are necessary for diagnosis of JS. Magnetic resonance imaging (MRI) has revolutionized the diagnosis of Joubert syndrome. It revealed the midbrain malformations included fourth ventricle dilatation and superior cerebellar peduncle elongation, which forms the classically described "molar tooth sign" (6). After the first months of life, global prognosis considerably varies among JS subgroups depending on the extent and severity of organs involvement (3). Here we describe three cases of JS in a family with mental and ocular presentations.

Case report
We want to report three children with JS in a family with the same presentations. The only healthy child is 6 years old. She has normal IQ and development, But her tooth eruption occurred after 1 years old. Her mother's tooth eruption had occurred in the same age. Proximal and distal forces are normal. Deep tendon reflexes are normal too, but toe to heal test is abnormal. Her bilateral ultrasonography is normal, and has no history of any considerable respiratory disorder. Case 2 She is a 10 years old girl with the same symptoms and signs as her sister, except some differences. She has developmental delay, FTT, mental retardation and decreased visual acuity in both eyes. She doesn't have aggressive behavior. Her development was as same as her sister. Neurologic examinations and laboratory and imaging results were also similar ( Figure 1).

Case 1
The first child of the family is a 12 years old girl, with history of developmental delay referred to Ghaem Medical Center for evaluation. Her mother recalls that the child could hold her head steady while sitting at age of one year and could sit independently at age of two years. She walked alone in age of four years. Tooth eruption occurred at age of one year. Bowel and bladder control emerged at age of four years. She also sufferes from mental retardation, failure to thrive (FTT), strabismus, decreased visual acuity in one eye and aggressive behavior. She can put the words together but is not able to make a complete sentence and is on speech therapy.

Case 3
He is a 3.5 years old boy, brother of the aforementioned cases, with developmental delay. He could hold his head steady while sitting at age of one year and could sit independently at age of two years; he has walked without help since 1 month ago. Tooth eruption occurred at age of one year. He still has urine and stool incontinence. He suffers from bilateral abducens nerve palsy. His limb forces and deep tendon reflexes were normal, but he had wide gait and ataxia (Figure 2).

Discussion
Joubert syndrome is a rare (an incidence of 1/100000) disorder of central nervous system Deepened interpeduncular fossa Elongated superior cerebellar peduncles malformation which is associated with joubert syndrome (Figure 3).
The brain MRI without contrast shows evidences of vermian dysgenesis and superior cerebellar peduncles representing the molar tooth midbrain-hindbrain  couldn't be performed and in only one of them that we could do MRI, molar tooth sign was seen that helped us to diagnose the syndrome. After one-year follow-up and rehabilitation, their abilities are much improved. We recommend that rehabilitation therapy can improve disabilities of patients with JS.